Capsaicin Inhibits Dimethylnitrosamine-Induced Hepatic Fibrosis by Inhibiting the TGF-β1/Smad Pathway via Peroxisome Proliferator-Activated Receptor Gamma Activation

• Published in: Journal of agricultural and food chemistry 2017-01, Vol.65 (2), p.317-326
• Main Authors: Choi, Jae Ho, Jin, Sun Woo, Choi, Chul Yung, Kim, Hyung Gyun, Lee, Gi Ho, Kim, Yong An, Chung, Young Chul, Jeong, Hye Gwang
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Capsaicin - pharmacology; Collagen Type I - metabolism; Dimethylnitrosamine - toxicity; Disease Models, Animal; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase Inhibitors - pharmacology; NF-kappa B - metabolism; PPAR gamma - metabolism; Rats, Sprague-Dawley; Smad Proteins - metabolism; Tissue Inhibitor of Metalloproteinase-1 - antagonists & inhibitors; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transforming Growth Factor beta1 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.6b04805

Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2.3 ± 0.1 to 1.0 ± 0.1) and Smad2/3 phosphorylation (from 1.5 ± 0.1 to 1.1 ± 0.1 and from 1.6 ± 0.1 to 1.1 ± 0.1, respectively) by activating Smad7 expression (from 0.1 ± 0.0 to 0.9 ± 0.1) via PPAR-γ induction (from 0.2 ± 0.0 to 0.8 ± 0.0) (p < 0.05). Furthermore, in HSCs, CPS inhibited the TGF-β1-induced increases in α-SMA and collagen type I expression, via PPAR-γ activation. These results indicate that CPS can ameliorate hepatic fibrosis by inhibiting the TGF-β1/Smad pathway via PPAR-γ activation.